Osteoclasts are bone-degrading cells that are formed through fusion of their monocytic precursors. Three distinct subsets
of monocytes have been identified in human peripheral blood: classical, intermediate, and non-classical monocytes. They are
known to play different roles in physiology and pathology, but their capacity to differentiate into osteoclasts and whether
inflammatory cytokines influence this differentiation is unknown. We hypothesized that classical, intermediate, and non-classical
monocytes generate functionally different osteoclasts and that they respond in different ways to the inflammatory cytokine
interleukin-17A (IL-17A). To investigate this, the different monocyte subsets were isolated from human peripheral blood and
osteoclastogenesis was induced with the cytokines M-CSF and RANKL, with or without IL-17A. We found that all subsets are able
to differentiate into osteoclasts in vitro, and that both osteoclastogenesis and subsequent bone resorption was distinctly
affected by IL-17A. Osteoclastogenesis and bone resorption by osteoclasts derived from classical monocytes remained unaffected
by IL-17A, while osteoclast formation from intermediate monocytes was inhibited by the cytokine. Surprisingly, bone resorption
by osteoclasts derived from intermediate monocytes remained at similar levels as control cultures, indicating an increased
bone resorbing activity by these osteoclasts. Limited numbers of osteoclasts were formed from non-classical monocytes on bone
and no bone resorption was detected, which suggest that these cells belong to a cell lineage different from the osteoclast.
By providing more insight into osteoclast formation from human blood monocytes, this study contributes to the possible targeting
of specific osteoclast precursors as a therapeutic approach for diseases associated with inflammatory bone loss

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